
RTG 2816
Non-canonical
G protein signaling pathways
Projects
Targeting the non-canonical G protein signaling via Girdin inhibition:
from ligand to tracer development

Girdin (GIV) is a key activator of Gi pro-teins that links RTK and GPCR signaling to PI3K-Akt activation and reduced cAMP levels, driving pro-cesses like cell migration and meta-stasis; its overexpres-
sion in cancers makes it a promising therapeutic target, and the recently discovered selective inhibitor IGGi-11 offers the first proof-of-concept for pharmacologically blocking Girdin-mediated tumor progression.
Dissecting non-canonical from canonical Gαi-dependent pathways in ischemia- reperfusion injury
Cardiovascular diseases and stroke belong to the leading cau-ses of death worldwide.

After ischemia, the subsequent reperfufusion process promotes a local inflammation mediated by infiltrating neutrophils and ROS, exacerbating tissue damage and leading to reperfusion injury. G protein signal transduction modulates cell recruitment into inflammatory tissue, however Gi-driven canonical vs. non-canonical contribution is still elusive.
Mode of action of the Gαi/ Gpsm2 and the RGS4 / neurabin complex in cochlear hair cells

During the development of the inner ear, Gai3 and its non-canonical regulator Gpsm2 play an essential role for orienting sensory hair cells. In addition, in the mature organ of Corti, Gai3 signalling is involved in protective mechanisms during noise trauma.
Modulation of heterotrimeric
G protein activity by nucleoside diphosphate kinase

Nucleoside diphosphate kinases (NDPKs) form complexes with heterotrimeric G proteins and provide GTP for the activation of these signal transducers. Thus, their function as activator of G protein signaling (AGS) is investigated in this project.
Platelet-derived stimulators of non-canonical neutrophil GPCR signaling in NETosis and thrombosis

Thrombo-occlusive disorders such as acute myocardial infarction, ischemic stroke and venous thromboembolism are still the leading cause for morbidity and mortality worldwide. The development and progression of these disorders is driven by a complex interplay of platelets and immune cells such as particularly neutrophils.



